1. Field of the Invention
This invention relates to a seamless capsule, and more particularly to techniques effectively applied to a seamless capsule capable of containing a large quantity of an active ingredient.
2. Statement of the Related Art
In general, hard capsules are employed for filling powdery material. However, with this hard capsules, there are presented the following problems. That is, firstly, the hard capsules are standardized their size and volume, even in a smallest capsule No. 5, the length thereof is as large as 1.2.about.1.4 cm, and hard capsules smaller than No. 5 can not be produced because of the standard and technical problem. Secondly, during the manufacturing of the capsules, such processes as encapsulating, cap coupling and the like are needed, so that the production efficiency is low. Thirdly, according to Japanese law, in the field of health foods, ingredients, with which the hard capsules are permitted to be encapsulated, are limited, so that types of products permitted to be on sale are limited.
On the other hand, although there are no such problems as described above for a seamless capsule and a soft capsule, such a problem is presented that, even in the case of these capsules, the capsules can not be encapsulated with the powder as it is. Then, there have been tried various methods for encapsulating the seamless capsules and the like with a powder material, which are not limited in dimensions and materials to be encapsulated. In these cases, it is conventional that the powder is dissolved in a solvent medium to provide a liquid solution, or the powder is suspended in a solvent medium to provide a fluid dispersion, which is encapsulated in a capsule.
In this case, as a solvent medium to be used, such one is desirable that a powder material as being an object can be dissolved at a high concentration, a stable solution can be obtained after the dissolution and no harm is given to human body. However, as for a powder material desired to be used, in fact, there are many cases where such a convenient and suitable solvent medium does not exist. Hence, in general, a powder material is enclosed in capsules in a state of a fluid suspension. Then, as techniques for encapsulating a capsule with this suspension, especially encapsulating a seamless capsule to enclose the suspension therein, there have been known several examples as shown in Japanese Patent Application Publication No. 68446/1993, Patent Application Publication No. 39193/1978, Patent Laid-Open No. 190916/1984, Patent Laid-Open No. 92616/1979 and so forth.
Here, in Patent Application Publication No. 68446/1993, there is disclosed a method, in which a stabilizer is added to freeze-dried powder of Lactobacillus bifidus suspended in hydrogenated oil having a melting point between 30.degree. C. and 45.degree. C. and a melting point range of less than 3.degree. C. encapsulated in a soft capsule. In this case, the hydrogenated oil having the small range of the melting point is used, whereby the suspension is hardened immediately, so that moisture in the shell of capsule is prevented from moving to Lactobacillus bifidus. Furthermore, in Patent Application Publication No. 39193/1978, there is disclosed a mononucleus double-wall capsule, whose nuclear portion (inner-most layer) is encapsulated with powder dispersed in oil, which is hardened about at 10.degree. C. With this arrangement, it becomes possible to form a material to provide a capsule, otherwise it should be impossible to form the material to provide a capsule with a seamless one-wall capsule.
Further, in Patent Laid-Open No. 190916/1984, there is disclosed a seamless capsule containing a filler obtained by dispersing in oil an inclusion compound, in which a hydrophilic substance is included in a clathrate inclusion compound. In this case, the hydrophilic substance is to be taken into the interior of cavity formed in the clathrate inclusion compound, an insoluble composite material is formed, and this clathrate inclusion compound is dispersed in oil to obtain a stable dispersion containing the hydrophilic substance, so that a capsule can be formed. On the other hand, in Patent Laid-Open No. 92616/1979, there is disclosed a bioavailability improving drug, in which a solid chemical agent which is difficultly soluble in water is dispersed in oil (at liquid room temperature), with which a seamless mini-capsule having a particle diameter of 1.about.3 mm is encapsulated.
Here, the inventors of the present invention have found that, when the capsule encapsulating therein the suspension is manufactured, if the fill of the suspension is increased, then, when liquid drops through a multiple nozzle, the outer shells of the capsules are broken and satisfactory capsules can not be formed.
Then, when the above-described conventional methods are examined from the above-described viewpoint, firstly, in Patent Application Publication No. 68446/1993, the hydrogenated oil having the melting point higher than the room temperature is used as encapsulated- in liquid, whereby the suspension is hardened immediately at the time of formation of a capsule, so that an outer shell is difficultly subjected to the influence of the moisture of suspension and no damage is caused to the capsule. However, in this method, the encapsulated liquid is in a solid state at the room temperature, so that all stage of manufacturing the capsule, i.e. preparation, storage and supplying thereof should be performed under heated conditions. For this, the active ingredient is easily deteriorated and the heating means is needed at all times. Further, a solvent medium for dispersion is limited to the hydrogenated oil, there is a case where the active ingredient may be precluded from being absorbed into the human body depending upon the type of the hydrogenated oil, and there is a case where it is not appropriate to apply this method. In addition, the content is hardened at the room temperature, whereby the capsule becomes opaque, so that the product seems ugly, and further, detection of defectives such as uneven shell thickness, damages and the like is difficult. Hence, this method is not used in general.
Next, in Patent Application Publication No. 39193/1978, the encapsulated liquid (nuclear portion) is doubly protected by an intermediate layer (inner layer) and an outer layer,. so that damages are uneasily caused to the outer shell. However, in this method, use of a triple nozzle is essential, so that the device become complicated and it is not easy to perform operational control. Furthermore, the double layered capsule is needed, so that such a disadvantage is presented that the fill of the encapsulated liquid is decreased as compared with a capsule having a particle diameter equal thereto.
Further, in Patent Laid-Open No. 190916/1984, such an arrangement is adopted that the clathrate inclusion compound is dispersed in the oil, whereby, when the quantity of the clathrate inclusion compound is increased, a problem of the outer shell damage is still presented. Furthermore, the active ingredient is limited to the hydrophilic substance, and it is necessary to add the inclusion material such as cyclodextrin by more than a quantity equal thereto. Accordingly, such a problem is presented that the types of the active ingredient to be used are limited, and further, the content of the active ingredient is also restricted. Furthermore, it takes much process to produce the clathrate inclusion compound, and further, the production efficiency is low.
On the other hand, in Patent Laid-Open No. 92616/1979, as the encapsulated liquid, there is used the active ingredient difficultly soluble in water to be molecularly dispersed (dissolved) and/or particulately dispersed and, as for the outer shell damage, conditions equal thereto are brought about. Further, in this case, only the one obtained by dissolution is described as an example, but, there is not described the embodiment of forming the capsule for the one dispersed particulately.
Then, the inventors of the present invention, paying their attention to the technique described in this Patent Laid-Open No. 92616/1979, have tried to form the capsule containing the encapsulated liquid not described in the example, in which the active ingredient is dispersed particulately. As the result, they have been confronted with the fact that, when it is tried to increase the containing ratio of the active ingredient, the outer shell breakage are often caused.